Screening of crosstalk and pyroptosis-related genes linking periodontitis and osteoporosis based on bioinformatics and machine learning

Abstract

Background and objectiveThis study aimed to identify crosstalk genes between periodontitis (PD) and osteoporosis (OP) and potential relationships between crosstalk and pyroptosis-related genes.MethodsPD and OP datasets were downloaded from the GEO database and were performed differential expression analysis to obtain DEGs. Overlapping DEGs got crosstalk genes linking PD and OP. Pyroptosis-related genes were obtained from literature reviews. Pearson coefficients were used to calculate crosstalk and pyroptosis-related gene correlations in the PD and OP datasets. Paired genes were obtained from the intersection of correlated genes in PD and OP. PINA and STRING databases were used to conduct the crosstalk-bridge-pyroptosis genes PPI network. The clusters in which crosstalk and pyroptosis-related genes were mainly concentrated were defined as key clusters. The key clusters’ hub genes and the included paired genes were identified as key crosstalk-pyroptosis genes. Using ROC curve analysis and XGBoost screened key genes. PPI subnetwork, gene–biological process and gene-pathway networks were constructed based on key genes. In addition, immune infiltration was analyzed on the PD dataset using the CIBERSORT algorithm.ResultsA total of 69 crosstalk genes were obtained. 13 paired genes and hub genes TNF and EGFR in the key clusters (cluster2, cluster8) were identified as key crosstalk-pyroptosis genes. ROC and XGBoost showed that PRKCB, GSDMD, ARMCX3, and CASP3 were more accurate in predicting disease than other key crosstalk-pyroptosis genes while better classifying properties as a whole. KEGG analysis showed that PRKCB, GSDMD, ARMCX3, and CASP3 were involved in neutrophil extracellular trap formation and MAPK signaling pathway pathways. Immune infiltration results showed that all four key genes positively correlated with plasma cells and negatively correlated with T cells follicular helper, macrophages M2, and DCs.ConclusionThis study shows a joint mechanism between PD and OP through crosstalk and pyroptosis-related genes. The key genes PRKCB, GSDMD, ARMCX3, and CASP3 are involved in the neutrophil extracellular trap formation and MAPK signaling pathway, affecting both diseases. These findings may point the way to future research.

Potential diagnostic markers and therapeutic targets for periodontitis and Alzheimer's disease based on bioinformatics analysis

“…[36][37][38] In recent years, research on the genes and mechanisms of common between periodontitis and other diseases has also gained attention. 39,40 Studying the interactions between diseases and their common biological mechanisms also contributes significantly to a clearer understanding of the diseases. Besides, the study of disease interactions is promising and significant for the prevention of major diseases.…”

“…Periodontitis is a common disease characterized by Pg infection, which is not only limited to oral health but also has a profound impact on other systemic diseases 36–38 . In recent years, research on the genes and mechanisms of common between periodontitis and other diseases has also gained attention 39,40 . Studying the interactions between diseases and their common biological mechanisms also contributes significantly to a clearer understanding of the diseases.…”

Exploring the molecular mechanisms of ferroptosis-related genes in periodontitis: a multi-dataset analysis

“…Programmed cell death encompasses apoptosis, necrosis, pyroptosis, and ferroptosis [ 24 , 25 ]. The roles of apoptosis, necrosis, and pyroptosis-related genes in the pathogenesis of periodontitis have been extensively studied and reported in the literature [ 26 – 29 ]. In contrast, while some reports have shed light on the significance of ferroptosis in the pathogenicity of periodontitis, the specific genes and molecular mechanisms involved remain insufficiently understood, necessitating further experimental and bioinformatics research [ 30 – 32 ].…”

Identification of crosstalk and immune related genes between Periodontitis and Rheumatoid Arthritis and construction of the ceRNA Network

“…That would add to the global economic burden and medical pressure of oral health. In recent years, PD was reported to relative to a series of systemic diseases, such as (Liu et al, 2022)osteoporosis, major depression disorder (Sun et al, 2021), diabetes (Polak and Shapira, 2018), coronary artery disease (Corredor et al, 2022) and rheumatoid arthritis(RA)(de Molon et al, 2019). Affecting multiple synovial membrane, rheumatoid arthritis is an autoimmune chronic in ammatory disease that leads to joint tissue destruction and functional disability (Ceccarelli et al, 2019).…”